The couch potato effect: Deletion of key muscle protein inhibits exercise

Nov 30, 2010

Daniel Kelly, M.D., and his colleagues at Sanford-Burnham Medical Research Institute (Sanford-Burnham) at Lake Nona have unveiled a surprising new model for studying muscle function: the couch potato mouse. While these mice maintain normal activity and body weight, they do not have the energy to exercise. In the December 1 issue of Cell Metabolism, Dr. Kelly's team reports what happens when muscle tissue lacks PGC-1, a protein coactivator that muscles need to convert fuel into energy.

"Part of our interest in understanding the factors that allow muscles to exercise is the knowledge that whatever this machinery is, it becomes inactive in , aging, diabetes and other chronic conditions that affect mobility," Dr. Kelly explained.

Normally, physical stimulation boosts PGC-1 activity in , which switches on that increase fuel storage, ultimately leading to "trained" muscle (the physical condition most people hope to attain through exercise). In obese individuals, PGC-1 levels drop, possibly further reducing a person's capacity to exercise – creating a vicious cycle. In this study, without muscle PGC-1 looked normal and walked around without difficulty, but could not run on a treadmill.

This video is not supported by your browser at this time.
Dr. Daniel Kelly describes how mice without the protein PGC-1 lose the ability to exercise. Credit: Josh Baxt

This is the first time that PGC-1 has been completely removed from muscle tissue, providing researchers with a new model to unravel the protein's role in muscle development, exercise and metabolism. So what happens to mice with muscles short on PGC-1? Their mitochondria – the part of the cell that converts fuel into energy – can't function properly, so cells have to work harder to stay vigorous. This extra effort rapidly depletes carbohydrate fuel stores, leading to premature fatigue. In short, PGC-1 is necessary for exercise, but not normal development and activity.

But these mice held another surprise. PGC-1-deficient couch potato mice were not obese and still respond normally to insulin – meaning they are not at risk for developing diabetes despite their sedentary lifestyles and mitochondrial problems. This was unexpected because many scientists believe that dysfunctional mitochondria trigger a cascade of insulin resistance and diabetes. This study dispels that notion, instead suggesting that perhaps malfunctioning mitochondria are a result of diabetes, rather than a cause.

"Lo and behold, even though these animals couldn't run, they showed no evidence of insulin resistance," Dr. Kelly said. "We are now investigating what happens when we boost PGC-1 activity intermittently, as normally occurs when a person exercises."

Explore further: The impact of bacteria in our guts

More information: Zechner C, Lai L, Fong JL, Geng T, Yan Z, Rumsey JW, Collia D, Chen Z, Wozniak DF, Leone TC, Kelly DP. Total skeletal muscle PGC-1 deficiency uncouples mitochondrial derangements from fiber type determination and insulin sensitivity. Cell Metabolism. December 1, 2010.

Provided by Sanford-Burnham Medical Research Institute

4.7 /5 (6 votes)

Related Stories

'Marathon mice' elucidate little-known muscle type

Jan 03, 2007

Researchers report in the January issue of the journal Cell Metabolism, published by Cell Press, the discovery of a genetic "switch" that drives the formation of a poorly understood type of muscle. Moreover, they found, animal ...

Power-boosting signal in muscle declines with age

Feb 06, 2007

As people age, they may have to exercise even harder to get the benefits afforded to younger folk. That's the suggestion of a report in the February issue of the journal Cell Metabolism, published by Cell Press, showing that a ...

Exercise pivotal in preventing and fighting type II diabetes

Feb 07, 2007

One in three American children born in 2000 will develop type II diabetes, according to the U.S. Centers for Disease Control and Prevention (CDC). A new study at the University of Missouri-Columbia says that acute exercise ...

Recommended for you

The impact of bacteria in our guts

Aug 22, 2014

The word metabolism gets tossed around a lot, but it means much more than whether you can go back to the buffet for seconds without worrying about your waistline. In fact, metabolism is the set of biochemical ...

Stem cell therapies hold promise, but obstacles remain

Aug 22, 2014

(Medical Xpress)—In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and ch ...

New hope in fight against muscular dystrophy

Aug 22, 2014

Research at Stockholm's KTH Royal Institute of Technology offers hope to those who suffer from Duchenne muscular dystrophy, an incurable, debilitating disease that cuts young lives short.

Biologists reprogram skin cells to mimic rare disease

Aug 21, 2014

Johns Hopkins stem cell biologists have found a way to reprogram a patient's skin cells into cells that mimic and display many biological features of a rare genetic disorder called familial dysautonomia. ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

gwrede
not rated yet Dec 01, 2010
Fat people get all the excuses for being fat. And scientists invent and discover new ones every month. But now, I have an excuse for being a couch potato!!!